Chembiochem. 2014 Jan 24;15(2):259-66. doi: 10.1002/cbic.201300527.
Within the framework of our genome-based program to discover new antibiotic lipopeptides from Pseudomonads, brabantamides A-C were isolated from plant-associated Pseudomonas sp. SH-C52. Brabantamides A-C displayed moderate to high in vitro activities against Gram-positive bacterial pathogens. Their shared structure is unique in that they contain a 5,5-bicyclic carbamate scaffold. Here, the biosynthesis of brabantamide A (SB-253514) was studied by a combination of bioinformatics, feeding experiments with isotopically labelled precursors and in vivo and in vitro functional analysis of enzymes encoded in the biosynthetic pathway. The studies resulted in the deduction of all biosynthetic building blocks of brabantamide A and revealed an unusual feature of this metabolite: its biosynthesis occurs via an initially formed linear di-lipopeptide that is subsequently rearranged by a novel FAD-dependent Baeyer-Villiger monooxygenase.
在我们基于基因组的方案框架内，从假单胞菌中发现新的抗生素脂肽，从与植物相关的假单胞菌 SH-C52 中分离出布拉班肽 A-C。布拉班肽 A-C 对革兰氏阳性细菌病原体表现出中等至高的体外活性。它们的共同结构是独特的，因为它们含有 5,5-双环氨基甲酸酯支架。在这里，通过生物信息学、用同位素标记的前体进行喂养实验以及对生物合成途径中编码的酶进行体内和体外功能分析，研究了布拉班肽 A（SB-253514）的生物合成。这些研究推断出了布拉班肽 A 的所有生物合成构建块，并揭示了这种代谢物的一个不寻常特征：其生物合成是通过最初形成的线性二脂肽进行的，然后通过一种新型的 FAD 依赖性 Baeyer-Villiger 单加氧酶进行重排。
